Pursuing the magic of science

By Nicole Lim, Senior editor
Wang in her lab in 2016
Wang Hongyan in her lab in 2016

Step into Wang Hongyan’s office and the first thing a visitor notices is a dark grey armchair tucked behind her desk. Like its owner, the chair is unassuming but exudes a quiet presence and purpose. Wang’s unexpected choice of chair also reflects a fresh perspective, with which she has built a formidable track record—and reputation—in neuroscience.

“When she publishes, her science is never questioned,” said Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, where Wang has been based since 2007. “With Hongyan, the story just keeps getting better.”

Last year, she became the first woman and only the third scientist from Singapore to be elected by members of the European Molecular Biology Organisation or EMBO as an associate member.

“I couldn’t believe it; it was such a nice surprise,” said Wang, a professor with the Neuroscience and Behavioural Disorders Programme.


Doing things her way

Wang has displayed an original streak from a young age. Growing up along the banks of the Yangtze River, Wang fondly recalls after-school adventures playing by the riverside, sliding down massive sand dunes at construction sites or hanging from the mooring lines of ships docked at the local port.

Her younger sister, Katherine, remembers an older sister who always had her own ideas, could transform bottle caps and other scraps into delicate works of art and inspired others to follow her. Katherine Wang, who is an associate director with the Health Services and Systems Research Programme at Duke-NUS, would even resort to invoking her older sister’s name to settle arguments with their friends.

“And the argument would stop at that,” she said. “Everyone looked up to her.”

Devoted to playing, Wang Hongyan wasn’t a top student, even though she is inherently bright. She simply did not see the point of completing homework when she already grasped what was being taught.

“I hated repeating the same thing,” she said.

Instead of revising, Wang would spend her time reading a novel, shoving the illicit reading quickly out of sight when her parents looked in.

“My parents probably knew what I was up to, but they never scolded me, and I really enjoyed the freedom they gave me,” added Wang.


Double doors to a world of ‘magic’

When Wang discovered a similar freedom in molecular biology as an undergraduate, she had at last found her passion.

While she was enrolled at the East China University of Science and Technology in Shanghai in the mid-1990s, Wang completed her final-year project across town at Fudan University, where the world of molecular biology widened for her.

She was hooked by the wonderful things that she could do with molecular cloning, which felt like discovering a new toy. “This was a magical world I had never been exposed to, full of mysteries that I wanted to get to the bottom of,” she said.

But Wang didn’t just discover her academic passion—she also met fellow neuroscientist, Yu Fengwei, who was at the time a master’s student in the same lab at the East China University.

“It was love at first sight,” said Yu, who soon moved to Singapore to pursue his PhD with the Institute of Molecular and Cell Biology.

Wang agrees: “Within a few months, I’d decided to marry him.”

Wang in the lab in Singapore in 1998
Wang in the lab in Singapore in 1998 // Credit: Wang Hongyan

Wang married Yu and followed him to Singapore, embarking on her PhD at Institute of Molecular Agrobiology that later became the Temasek Life Sciences Laboratory. For her first rotational project, Wang approached Professor Mohan Balasubramanian, who is now Pro-Dean at the University of Warwick, to take her on.

Even as he interviewed her, Balasubramanian was impressed by her intellect and solid understanding of the science. When it took Wang the same amount of time to perform an experiment where she had to cross yeast strains as it would an experienced colleague, Balasubramanian knew the tables had turned.

“The way she understood genetics and cell biology was unbelievable,” said Balasubramanian, Wang’s former mentor and now lifelong friend. “Within a week, I knew that I wanted her in my lab.”


Pursuing her passion

Her postgraduate years were a transformative time for Wang, who says that she became a workaholic.

“When I entered the PhD programme, my life changed. I voluntarily gave up my interests because the projects were so interesting and exciting,” she said. Wang was regularly the last to leave the lab, marking her exit by switching off the lights as she trudged home. “Mohan’s passion for research and his innovative ideas have had the biggest scientific impact on me, shaping who I am.”

Following her PhD, she moved to developmental biologist William Chia’s lab, where she first started working with fruit flies to study the asymmetric division of neural stem cells. While there, she found a genetic mutant that caused fruit flies’ brains to swell to ten times their expected size, cramming them full of neural stem cells.

Wang studies asymmetric division of neural stem cells
Wang studies asymmetric division of neural stem cells. In this image, an apical protein is stained red, a basal protein in green and DNA in blue in wild type neural stem cells. 

“I was totally fascinated by this new phenotype,” said Wang, who was determined to understand the bigger picture by quantifying the number of neural stem cells present in the phenotype and how that related to the asymmetrical division defect. During this project, she discovered a protein that behaves like a tumor suppressor by regulating the asymmetric division.

“I was sure that there was something totally new and exciting there as I could use Drosophila neural stem cells as a new model to study brain tumor suppressors,” said Wang, who also had her first child during that time—a daughter, who is now 16 years old. With the support of her parents, Wang and her husband were able to balance the demands of a life in science with a young family.

“She juggles her commitments very well: dealing with her work, taking care of the kids. She is very efficient. Scientifically, she is very sharp and passionate and sacrificed a lot of free time to work in the lab,” said Yu.

Wang was in the driving seat for most of her work on brain tumor suppressors, from asking the questions to submitting her manuscripts. She credits the freedom, generosity, and unwavering support of Chia that enabled her to take ownership of her projects during these post-doc years.

“‘I’m fine with whatever decision you make. Just go ahead with it’—those were Bill’s usual replies when I’d ask for his advice,” recalled Wang.

Both Balasubramanian and Chia were inspirational role models for Wang, who tries to similarly pay it forward. And Wang’s post-docs, Deng Qiannan and Mahekta Rajeshkumar Gujar, value that.

“She is an excellent mentor, who’s inspired me to lead a team one day,” said Deng.

The two post-docs not only honed their skills, learned new techniques and pursued their own projects but also had fun and felt cared for as part of Wang’s team.

“She puts you on the right path so that you can finish and advance your career with the papers you publish in her lab,” said Gujar, who is still deciding whether to pursue an independent research career.


An independent fruit fly researcher at a medical school

When it was time to pursue an independent research career, Wang applied to an advertisement from a new medical school that was recruiting its first assistant professors.

“We received maybe 30 to 40 applications and Hongyan’s application percolated to the top pretty quickly because she was a young scientist on the path up,” said Casey.

Despite her lack of experience in mammalian models, Casey and the hiring committee at Duke-NUS saw the relevance of Wang’s work in fruit flies to a young medical school that was keen to make a name for itself in the area of neuroscience.

And Casey did not have to wait long to be proven right. Within a year from her appointment and shortly after the birth of her second daughter, Wang received the Young Scientist Award. When she received the award, she shared the stage with Balasubramanian who received the National Science Medal.

“You get the most satisfaction from seeing the people you trained go on to do wonderful things in many fields and that’s what she’s doing,” said Balasubramanian, who has trained about 50 scientists during his career and counts Wang in the top echelon of that group.

By this time, Wang’s reputation was already preceding her. The cell and developmental biologist Cayetano González, who leads the Cell Division group at the Institute for Research in Biomedicine in Barcelona, remembers his first interaction with her: an email from Wang introducing herself and inviting him to speak at a seminar at Duke-NUS.

“I immediately wrote back to say she didn’t need an introduction,” said González, who accepted the invitation to speak and has since become a long-time collaborator and friend.

It was also González who nominated Wang for EMBO membership last year. When he received the call for nominations as an EMBO member, he knew whom to put forward.

“Hongyan has been in my mind for membership for some time because she has made extraordinary contributions to the field of neural stem cell development,” said González.

For associate members who work outside of Europe to be elected, the bar is often even higher as only a handful of associate memberships are given out. But Wang’s nomination sailed through.

“Every year, many deserving candidates are left out and this only adds to the privilege of being elected and to Hongyan’s achievement,” added González.


Shaping a future beyond herself

Since joining Duke-NUS 13 years ago, Wang has expanded her research. She still detests doing the same thing, so she constantly looks for new, but complementary, directions. In this way, she has moved from asymmetric division to dedifferentiation and most recently turned her focus on neural stem cell reactivation.

Joining Duke-NUS has also had a big impact on her research. From being focused on her model system, she has become much more aware of the potential applications of her work to clinical care. She’s also expanded the model systems that she uses and now works with mouse models and human mini-brains in addition to fruit flies.

“In the next 20 years, I want to focus on neurodevelopmental disorders because these affect about five per cent of all kids in Singapore,” said Wang, who has begun to work with clinician partners to use her mini-brain models to study mutations that are associated with neurodevelopmental disorders.

“Once we know the mutations that cause neurodevelopmental disorders, hopefully, we can develop gene therapy that allows us to replace the mutated genes with its wildtype original,” added Wang.

Wang (right) with Yu (left) and their two daughters on a holiday in 2018

Wang (right) with Yu (left) and their two daughters in 2018 // Credit: Wang Hongyan

While Wang used to work long hours, particularly during the early days of her lab, she now makes a point to spend evenings with her family. Last year’s Circuit Breaker and gradual lifting of restrictions also meant more time with her now teenaged daughters.

“We worked side-by-side during that time, and that was great,” said Wang, who is very proud that both her daughters are STEM (science, technology, engineering and mathematics) girls.

She is also a great advocate and supporter of the wider neuroscience community in Duke-NUS in her capacity as the deputy director of the Neuroscience and Behavioural Disorders Programme as well as through her involvement in the wider community in Singapore and beyond. Her rigorous approach to science and continuous pursuit of new knowledge have also made her a sought-after speaker and reviewer.

“Whenever I ask her to review papers, she gives the most critical yet supportive reviews of people’s research work,” said Balasubramanian who is an editor for several journals including Current Genetics and eLife.

The fact that she achieves all this from an armchair in her office—and its identical twin in her home office—continues to amaze her husband. “I would be so ineffective in a chair like that!” laughs Yu. “But she becomes even more focused.”

To an outsider, scientific research may epitomise repetition, but for Wang, the promise of new discoveries remains tantalising.

“We ask different questions, we expect different results and, sometimes, we don’t know what to expect. And that is the most fun part,” said Wang. “If not every day, then every week, we discover something new that brings excitement. I like new things.”